In Context
Profile Ian Gilron: pain killer “Early on it seemed like in neuroscience, pain was the field that had the most unanswered questions” says Ian Gilron, explaining his decision to devote his creative energy to a problem that has been with us since the dawn of humanity: how to effectively and safely relieve our pain. Just into his 40s, Gilron is already an “international star in the pain field as a clinical scientist”, according to Dwight Moulin, the Earl Russell Chair of Pain Medicine at the University of Western Ontario, ON, Canada. And although a lot of the questions that he encountered when he started out remain unanswered, Gilron is feeling positive about the future. “We probably need a little more optimism”, said the smiling, affable Canadian when the Lancet Neurology caught up with him in September. With Gilron’s sunny disposition, optimism seems to be something that comes naturally; but not everyone shares his outlook. In neuroscience generally, and in pain research especially, the past few years have seen a venting of frustration at disappointing clinical results, with many pointing the finger at perceived failings at the preclinical stage. “We probably need to back away from that and really try to look at some of the benefits of research that have come through”, Gilron explains. His studies of combination pharmacotherapy are an excellent example. “Elegant and very difficult to carry out”, says Moulin, “they shed considerable light on the role of polypharmacy in pain management”. As Director of Clinical Pain Research at Queen’s University in Ontario, Gilron and coworkers have been studying the effect of the widespread practice of prescribing multiple pain drugs for patients with poorly managed chronic pain. “We have engaged in polypharmacy on a regular basis for decades without really knowing what we were doing or the expected outcome”, notes Moulin, and it has become a public health issue. “Polypharmacy is a double-edged sword”, explains Gilron. “If it is carefully instituted and done in a rational manner, it can provide more benefit, but on the other hand, it can be the source of more serious side-effects.” Two drugs are not necessarily better than one, with evidence that many combinations can result in more serious side-effects without improved pain management, and Gilron predicts a lot of headway will be made by going from clinical practice back to clinical research, and even back to the laboratory to look further into the effects of combination therapy. “The next 5 years are going to be very exciting”, he explains: “a lot of potential benefits can be found not just by improving pain management but by improving safety, and a lot of work needs to be done and can be done by looking at commonly used combinations in the clinic and then really confirming or refuting the evidence of benefit for those combinations”. www.thelancet.com/neurology Vol 12 November 2013
Although optimistic, Gilron is also a realist. Splitting his time between research and clinical work, he has come to the realisation that although his research is “directly related to humans, and involves humans, the bridge between the research we’re doing and practice is huge. To think that the results of a clinical trial are going to translate directly to prescription pathways that physicians can go ahead and use is an overstretch.” Many factors are involved in deciding how and when to implement a certain treatment intervention, and so much variation exists between individuals, that the issue is “where do you start”, he says. “Individualised medicine is here to stay, but it’s not going to go any further without the basic clinical research to identify more effective treatment interventions which could be helpful in the first place”. Pain is an incredibly complex, multifaceted problem to unravel. On the one hand, it is a result of a sensory discriminative process to enable a noxious stimulus to be located and dealt with, but on the other, there is a more subjective and difficult to define emotional and motivational aspect. It is a dichotomy that Gilron says mirrors his own academic split personality—never able to choose between science and maths and his passion for the more creative arts. It was during his training as an anaesthesiologist at McGill University (Montreal, QC, Canada), that Gilron first met Ron Melzack; one of the founding fathers of the pain community. After doing some basic laboratory research under the guidance of Terry Coderre and Remi Quirion, he realised that “most of the questions that were burning in my mind related to humans and to the clinical management of pain”, so when the opportunity to work with Mitchell Max at the National Institutes of Health in the USA came up, Gilron jumped at the chance. “What was meant to be a 1 year fellowship turned into 3 years learning how to design and conduct controlled trials and learn more about treatment response”, he recalls, and it provided a perfect outlet for his creative impulses. “Clinical trials sound like the least creative thing, and a lot of it is bean counting, but the creativity comes in thinking about the questions”, he says. Focused, tenacious, and rigorous, Gilron “represents the future” says Peter Watson, a neurologist at the University of Toronto, ON, Canada. And, according to Gilron, the future of pain research is bright. “The pain research community has become highly evolved, and there’s a lot of reason to be optimistic and not always look at how much of the problem remains unsolved, but to realise that a lot of our tools have become very sophisticated”, he says. “We just don’t know when the game changer might come”.
See Review page 1084
David Holmes 1045
Profile Ian Gilron: pain killer “Early on it seemed like in neuroscience, pain was the field that had the most unanswered questions” says Ian Gilron, explaining his decision to devote his creative energy to a problem that has been with us since the dawn of humanity: how to effectively and safely relieve our pain. Just into his 40s, Gilron is already an “international star in the pain field as a clinical scientist”, according to Dwight Moulin, the Earl Russell Chair of Pain Medicine at the University of Western Ontario, ON, Canada. And although a lot of the questions that he encountered when he started out remain unanswered, Gilron is feeling positive about the future. “We probably need a little more optimism”, said the smiling, affable Canadian when the Lancet Neurology caught up with him in September. With Gilron’s sunny disposition, optimism seems to be something that comes naturally; but not everyone shares his outlook. In neuroscience generally, and in pain research especially, the past few years have seen a venting of frustration at disappointing clinical results, with many pointing the finger at perceived failings at the preclinical stage. “We probably need to back away from that and really try to look at some of the benefits of research that have come through”, Gilron explains. His studies of combination pharmacotherapy are an excellent example. “Elegant and very difficult to carry out”, says Moulin, “they shed considerable light on the role of polypharmacy in pain management”. As Director of Clinical Pain Research at Queen’s University in Ontario, Gilron and coworkers have been studying the effect of the widespread practice of prescribing multiple pain drugs for patients with poorly managed chronic pain. “We have engaged in polypharmacy on a regular basis for decades without really knowing what we were doing or the expected outcome”, notes Moulin, and it has become a public health issue. “Polypharmacy is a double-edged sword”, explains Gilron. “If it is carefully instituted and done in a rational manner, it can provide more benefit, but on the other hand, it can be the source of more serious side-effects.” Two drugs are not necessarily better than one, with evidence that many combinations can result in more serious side-effects without improved pain management, and Gilron predicts a lot of headway will be made by going from clinical practice back to clinical research, and even back to the laboratory to look further into the effects of combination therapy. “The next 5 years are going to be very exciting”, he explains: “a lot of potential benefits can be found not just by improving pain management but by improving safety, and a lot of work needs to be done and can be done by looking at commonly used combinations in the clinic and then really confirming or refuting the evidence of benefit for those combinations”. www.thelancet.com/neurology Vol 12 November 2013
Although optimistic, Gilron is also a realist. Splitting his time between research and clinical work, he has come to the realisation that although his research is “directly related to humans, and involves humans, the bridge between the research we’re doing and practice is huge. To think that the results of a clinical trial are going to translate directly to prescription pathways that physicians can go ahead and use is an overstretch.” Many factors are involved in deciding how and when to implement a certain treatment intervention, and so much variation exists between individuals, that the issue is “where do you start”, he says. “Individualised medicine is here to stay, but it’s not going to go any further without the basic clinical research to identify more effective treatment interventions which could be helpful in the first place”. Pain is an incredibly complex, multifaceted problem to unravel. On the one hand, it is a result of a sensory discriminative process to enable a noxious stimulus to be located and dealt with, but on the other, there is a more subjective and difficult to define emotional and motivational aspect. It is a dichotomy that Gilron says mirrors his own academic split personality—never able to choose between science and maths and his passion for the more creative arts. It was during his training as an anaesthesiologist at McGill University (Montreal, QC, Canada), that Gilron first met Ron Melzack; one of the founding fathers of the pain community. After doing some basic laboratory research under the guidance of Terry Coderre and Remi Quirion, he realised that “most of the questions that were burning in my mind related to humans and to the clinical management of pain”, so when the opportunity to work with Mitchell Max at the National Institutes of Health in the USA came up, Gilron jumped at the chance. “What was meant to be a 1 year fellowship turned into 3 years learning how to design and conduct controlled trials and learn more about treatment response”, he recalls, and it provided a perfect outlet for his creative impulses. “Clinical trials sound like the least creative thing, and a lot of it is bean counting, but the creativity comes in thinking about the questions”, he says. Focused, tenacious, and rigorous, Gilron “represents the future” says Peter Watson, a neurologist at the University of Toronto, ON, Canada. And, according to Gilron, the future of pain research is bright. “The pain research community has become highly evolved, and there’s a lot of reason to be optimistic and not always look at how much of the problem remains unsolved, but to realise that a lot of our tools have become very sophisticated”, he says. “We just don’t know when the game changer might come”.
See Review page 1084
David Holmes 1045
